This invention relates to a flexible backing for a composition for administration of drugs through the skin.
With increasing frequency, pharmacologically active agents have been administered by application to the skin, often in a solid carrier. The drug is incorporated into the carrier and attached to the skin, typically by means of an adhesive. The carrier can be a gel or a more rigid polymer or combination of polymeric substances and can have single or multiple components. The adhesive can also function as the carrier. One side of the carrier is applied to the skin, while the other side is accessible to the environment.
Typically, a backing is present on the side of the carrier accessible to the environment. The backing limits the passage of substances from the carrier into the environment, and limits the reverse passage of substances from the environment into the carrier. Typically, the backings are composed of metal foil, metallized plastic, or single or multiPle layers of a polymeric (plastic) substances which do not permit the passage of more than negligible amounts of water.
One known carrier, namely the Bolar Pharmaceutical Co. transdermal preparation for nitroglycerin sold under the trademark NTS, contains a backing material containing polyvinyl chloride. Other backing materials used in transdermal preparations marketed in the United States include aluminized polyester (Transderm Scopolamine, CIBA); other aluminized plastics are used in Transderm Nitro (CIBA); Deponit (Wyeth); and Catapress-TTS (Boehringer Ingelheim.). Aluminum foil (Nitro-Dur, Key; Nitrodisc, Searle), polyethylene/ polyvinylidene chloride coextrusion (Nitro-Dur II, Key), and Polyester (Estraderm, CIBA) are also used.
Aluminum containing backing materials have negligible moisture vapor transmission rates. Aluminum foil, as reported in "Aluminum Foil" by the Aluminum Association, Inc., page 5, Table 3, Second Edition, January 1981, is impermeable to moisture at a thickness of one mil (0.001 inch) and thicker. The water vapor transmission rate is 0.02 grams or less/100 square inches in 24 hours at 100 degrees Fahrenheit (.degree. F.) for a foil of 0.00035 inches, a commonly used thickness. When 0.00035 inch foil is laminated, the water vapor transmission rate drops to practically zero.
Other films common to the film industry, not necessarily to transdermals, which in principle are applicable to transdermals are polyethylene and ethylene copolymers, linear low density polyethylene, very low density polyethylene, ethylene methyl acrylate, ethylene vinyl acetate, polypropylene, polystyrene, polyurethane, polyvinyl and vinyl copolymers, and vinylidene chloride polymers and copolymers (Sarans).
Other available plastic films include:
Acetal PA0 Acrylic PA0 Acrylonitrile Butadiene Styrene (ABS) PA0 Acrylonitrile (Methyl Methacrylate/MMA) Copolymer PA0 Acrylonitrile Copolymer, Biaxially-Oriented PA0 Acrylonitrile Types, Other PA0 Ethylene Ethyl Acrylate (EEA) PA0 Ethylene Methyl Acrylate (EMA) PA0 Ethylene Vinyl Acetate (EVA) PA0 Ethylene Vinyl Acetate (EVA) Copolymer PA0 Ethylene Vinyl Alcohol (EVOH) Polymer PA0 Ionomers PA0 Nylon (Polyamide) PA0 Nylon (Polyamide), Biaxially-Oriented PA0 Nylon (Polyamide), Monoaxially-Oriented PA0 Nylon (Polyamide) Copolymer PA0 Polybutylene (PB) PA0 Polycarbonate (PC) PA0 Polyester PA0 Polyester, Oriented PA0 Polyester, Thermoplastic (Polyethylene TerePhthalate) (PET) PA0 Polyester, Thermoplastic Copolymer (PET-G) PA0 Polyethylene, High Density (HDPE) PA0 Polyethylene, High Density (HDPE), Oriented PA0 Polyethylene, High-Molecular-Weight, High Density (HMWHDPE) PA0 Polyethylene, Intermediate-Molecular-Weight, High Density (IMWHDPE) PA0 Polyethylene, Linear Low Density (LLDPE) PA0 Polyethylene, Low Density (LDPE) PA0 Polyethylene, Medium Density (MDPE) PA0 Polyethylene Oxide PA0 Polyimide PA0 Polypropylene (PP) PA0 Polypropylene (PP), Coated PA0 Polypropylene, Oriented (OPP) PA0 Polystyrene (PS) PA0 Polyurethane (PU) PA0 Polyvinyl Acetate (PVAC) PA0 Polyvinyl Chloride (PVC) PA0 Polyvinylidene Chloride (PVDC) PA0 Styrene Acrylonitrile (SAN)
Backings previously used for transdermal compositions typically consist of a polymer alone or laminated to a metal foil which is substantially impervious to moisture and gas, and thus not "breathable" in the sense of permitting permeation of water vapor to and from the composition. The result of this lack of breathability is a tendency of the formulation to irritate the skin or to tend to detach from the skin or both.
The backing must be sufficiently flexible to permit movement of the skin and be compatible with the carrier and drug in the sense that the carrier or the drug does not substantially degrade the backing, especially under normal conditions of use and storage for one to two years. The backing should also not substantially degrade the drug or the carrier.
The general theory of permeation of a gas or a liquid through a polymer matrix is that permeation is a product of the diffusion time and solubility constant of the permeant in the polymer matrix, both of which are often independent of each other. Very often, the property which results in a good gas barrier results in a poor water barrier. For example, highly polar polymers such as those containing hydroxyl groups (ethylene vinyl alcohol) are excellent gas barriers but poor water barriers. Conversely, non-polar hydrocarbon polymers such as polyethylene have excellent water barrier properties but poor gas barrier properties.
In order to be a good barrier polymer, the material should have some degree of polarity, chain stiffness, inertness, close chain-to-chain packing, some bonding or attraction between chains and a high glass transition temPerature (Tg). The various types of barrier polymers and their uses are thoroughly discussed in Salame, et al., "Barrier Polymers", Polym.-Plast. Technol. Eng. 8(2), 155-175 (1977). Not only does the functional group have an effect on oxygen permeability, but so does the degree of crystallinity, the degree of orientation of Polymer Chains, the inclusion of fillers and additives and the presence of moisture in the polymer. As a rule of thumb, permeation increases by 30 to 50% for every 5 degrees Celsius (C.degree.) temperature rise. Rate of permeation is also affected by the molecule, the molecular shape and the polarity of the permeating species.